5-bromo-1H-indazole → 2,2,2-trifluoro-1-(1H-indazol-5-yl)-1-(1-methyl-1H-indol-3-yl)ethanol

HRID 244407

Reaktionsgleichung

Reaktionsgleichung von HRID 244407
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.C([Li])CCC.[F:16][C:17]([F:31])([F:30])[C:18]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]([CH3:29])[CH:21]=1)=[O:19]>CCOCC>[F:31][C:17]([F:16])([F:30])[C:18]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2)([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]([CH3:29])[CH:21]=1)[OH:19]

Komponenten

5

Edukt 3

HCID 7619295-bromo-1H-indazoleHCID 35243881-Methyl-3-(trifluoroacetyl)-1H-indoleHCID 178418339Butyllithium

Produkt 1

HCID 594372242,2,2-trifluoro-1-(1H-indazol-5-yl)-1-(1-methyl-1H-indol-3-yl)ethanolAusbeute 26,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel

Versuchsvorschrift

To a chilled (−78° C.) solution of 1.5 g (7.61 mmol) of 5-bromoindazole in 15 mL ether was added 9.2 mL (23.0 mmol) of a 2.5 M solution of n-butyllithium in hexanes. After 5 minutes, the cold bath was removed and the mixture stirred 6 hours at room temperature. The mixture was cooled to −78° C. and 3.5 g (15.4 mmol) of 2,2,2-trifluoro-1-(1-methyl-1H-indol-3-yl)ethanone in 4 mL of a 1:1 mixture of ether-THF was added. The mixture was stirred overnight while warming to room temperature and was then quenched with aqueous ammonium chloride and extracted with ether. The organic layer was washed with water, brine, and dried over magnesium sulfate. Removal of the volatiles in vacuo provided a residue which was purified by CombiFlash chromatography using 0-90% EtOAc-hexanes (product eluted at 35% EtOAc) to afford 700 mg (26%) of 2,2,2-trifluoro-1-(1H-indazol-5-yl)-1-(1-methyl-1H-indol-3-yl)ethanol as a pale yellow foam.

Aufarbeitung

  1. customthe cold bath was removed
  2. temperatureThe mixture was cooled to −78° C.
  3. additionwas added
  4. stirringThe mixture was stirred overnight
  5. temperaturewhile warming to room temperature
  6. customwas then quenched with aqueous ammonium chloride
  7. extractionextracted with ether
  8. washThe organic layer was washed with water, brine
  9. dry with materialdried over magnesium sulfate
  10. customRemoval of the volatiles in vacuo
  11. customprovided a residue which
  12. customwas purified by CombiFlash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7cf7421ef3f14f2b92ef084ca90daccd
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658637B2

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